Non-motor asymmetry and dopamine degeneration in Parkinson’s disease DOI Creative Commons
Frederik Hansen, Karoline Knudsen, Malene Flensborg Damholdt

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 7(1)

Published: Dec. 24, 2024

Abstract Asymmetric dopaminergic degeneration of the striatum is a characteristic feature Parkinson’s disease, associated with right–left asymmetry in motor function. As such, studying provides insights into progressive neurodegeneration between cerebral hemispheres. Given impact Lewy pathology on various neurotransmitter systems beyond dopaminergic, it may be that other neuronal predominantly affected hemisphere are similarly affected. According to this hypothesis, would expected coincide systems. Consequently, functions primarily dependent integrity, such as function, should correlate bilateral non-motor rely systems, pupillary Therefore, study tested whether measures correlates striatal integrity. We also asymmetric greater overall. Using comparative cross-sectional design, we recruited newly diagnosed patients disease right-sided (n = 18), left-sided 15) or symmetric nigrostriatal denervation assessed dopamine PET. Detailed examinations lateralized function included lacrimation, hand skin wrinkling, salivation, olfaction and Healthy controls were for comparison. observed moderate-to-strong correlation putamen binding redilation speed [Spearman’s rank coefficient (rs) −0.53, 95% confidence interval (−0.77; −0.14), P 0.0084]. moderate correlations non-negative putaminal lacrimation [rs 0.35, (−0.00; 0.62), 0.0464] word recognition 0.36, (0.01; 0.63), 0.0410]. However, none significant after false discovery rate correction. group differences salivation (P 0.0390, ANOVA) trend towards participants loss compared healthy 0.0330, unadjusted). Additionally, showed greater, though non-significant, all those binding. In conclusion, contributes our understanding progression suggests link related autonomic particularly While findings do not support strict hemispheric association degeneration, potential relationships exist these features asymmetrical cholinergic.

Language: Английский

Toward alpha‐synuclein seed amplification assay in clinical practice DOI Creative Commons
Mathieu Verdurand,

Flora Kaczorowski,

Sophie Dautricourt

et al.

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 1, 2025

Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents facilitate its clinical implementation. Routine care CSF samples from 126 patients, comprising 47 with Lewy body diseases (LBD) (41 dementia bodies, six Parkinson's disease), 37 without alpha-synucleinopathy, and 42 Alzheimer's disease (AD), underwent assessment activity. showed sensitivity 72.3% specificity 100% when distinguishing clinically diagnosed LBD patients those alpha-synucleinopathy. In AD 14.3% were tested positive aSyn. The commercial-only exhibited excellent applied real-life cohort, signaling progress toward an aSyn biomarker settings. Diagnosis through lacks accessibility.This has satisfactory cohort.A negative does not completely exclude synucleinopathy.Some technical points must be considered developing aSyn-SAA.aSyn-SAA confined expert laboratories prion-like risk management.

Language: Английский

Citations

1
In vivo detection of Alzheimer's and Lewy body disease concurrence: Clinical implications and future perspectives DOI Creative Commons
Simone Baiardi, Oskar Hansson, Johannes Levin

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5757 - 5770

Published: June 21, 2024

Abstract INTRODUCTION The recent introduction of seed amplification assays (SAAs) detecting misfolded α‐synuclein, a pathology‐specific marker for Lewy body disease (LBD), has allowed the in vivo identification and phenotypic characterization patients with co‐occurring Alzheimer's (AD) LBD since early clinical or even preclinical stage. METHODS We reviewed studies an biomarker‐based diagnosis AD‐LBD copathology. RESULTS Studies large cohorts cognitively impaired individuals have shown that cerebrospinal fluid (CSF) biomarkers detect coexistence AD LB pathology approximately 20%–25% them, independently primary diagnosis. Compared to those pure AD, showed worse global cognition, especially attentive/executive visuospatial functions, motor functions. In unimpaired individuals, concurrent pathologies predicted longitudinal cognitive progression faster worsening memory, DISCUSSION Future research aiming better precision medicine approach should develop SAAs further reach quantitative evaluation staging each underlying using single biofluid sample. Highlights α‐Synuclein provide specific (LBD). allow (AD). coexist 20‐25% elderly ∼8% asymptomatic. causes is associated attentive/executive,

Language: Английский

Citations

7
Temporal Changes in Alzheimer's Disease‐Related Biomarkers in the CSF of Cognitively Normal Subjects at Different Ages: The Chongqing Ageing and Dementia Study DOI Creative Commons
Weiwei Li, Dong‐Yu Fan, Qi Sun

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

ABSTRACT Revealing the temporal evolution of cerebrospinal fluid (CSF) biomarkers during aging is critical to understanding disease pathogenesis and developing early diagnoses interventions for Alzheimer's (AD). CSF was obtained from 549 cognitively normal subjects between 18 93 years age. 12 AD‐related were evaluated, including amyloid β (Aβ42, Aβ40, Aβ42/Aβ40 ratio), hyperphosphorylated tau (P‐tau), neuronal injury/degeneration (T‐tau, NFL, NSE, H‐FABP, VILIP‐1), neuroinflammation (YKL‐40, TREM2), α‐synuclein (α‐synuclein). Associations these age as well apolipoprotein E ( APOE ) ε4 status associations among assessed. Aβ42, P‐tau, T‐tau levels exhibited nonlinear with age, which Aβ42 significantly modulated by status. Specifically, an accelerated decline in occurred at 45.69 ε4+ group, almost 23 earlier than that ε4− group (68.02 years). The age‐related change pattern P‐tau similar T‐tau, both increasing slightly but showing ≈60 group. All other except linearly associated had no effect on associations. Most positively correlated each ratio. varies throughout adult lifespan, allele modifying changes levels, potentially influencing levels.

Language: Английский

Citations

0
In vivo-measured Lewy body pathology is associated with neuropsychiatric symptoms across the Alzheimer’s disease continuum DOI
Douglas Teixeira Leffa, Guilherme Povala, Pâmela C.L. Ferreira

et al.

Published: March 26, 2025

Intracellular alpha-synuclein aggregates, known as Lewy bodies (LB), are commonly observed in Alzheimer's disease (AD) dementia. Post-mortem studies have shown a higher frequency of neuropsychiatric symptoms among individuals with AD and LB co-pathology. However, the effects vivo-measured pathology on remain underexplored. This study aimed to evaluate cross-sectional longitudinal across continuum. We analyzed data from 1,169 participants Disease Neuroimaging Initiative (ADNI). Participants had vivo measures (assessed using an seed amplification assay), amyloid-beta (Aβ) phosphorylated tau (p-tau) levels cerebrospinal fluid (CSF), evaluated Neuropsychiatric Inventory-Questionnaire (NPI-Q). Logistic Cox proportional hazards regression models were used assess effects, respectively, adjusting for age, sex, cognitive status. mean baseline age 73.05 (SD 7.22) years, 47.13% women, 426 (36.44%) cognitively unimpaired, 743 (63.56%) impaired. In analyses, was associated rates anxiety, apathy, motor disturbances, appetite disturbances. increased risk developing psychosis anxiety. These independent Aβ p-tau. Our results suggest that is closely findings underscore potential detection marker identifying at symptoms, both clinical trials practice.

Language: Английский

Citations

0
What Can We Learn About Alzheimer’s Disease from People with Down Syndrome? DOI
L. Maure Blesa, Íñigo Rodríguez‐Baz, María Carmona‐Iragui

et al.

Current topics in behavioral neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
The Effect of Amyloid and Tau Co-Pathology on Disease Progression in Lewy body Dementia: A Systematic Review DOI Creative Commons
Jerry Tan, A. Laurell, Emad Sidhom

et al.

Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 131, P. 107255 - 107255

Published: Dec. 24, 2024

Co-morbid Alzheimer's disease (AD) pathology (amyloid-beta and tau) is commonly observed in Lewy body dementia (LBD), this may affect clinical outcomes. A systematic review of the effect AD co-pathology on longitudinal outcomes LBD was conducted. search MEDLINE EMBASE (October 2024) yielded n = 3558 records that were screened by two independent reviewers. Included studies (n 31) assessed neuropathologic examination 10), positron emission tomography (PET) imaging 7), cerebrospinal fluid (CSF) 8) or plasma biomarkers 6); reported including cognitive functional decline, mortality, treatment response. Most neuropathology, PET reviewed demonstrated poorer prognosis + compared to LBD-, but discrepant findings seen among CSF studies. No included study better LBD+. The risk bias with Quality Prognosis Studies tool. All rated as low 12) presence (LBD+) associated accelerated decline 7/7), 3/3), greater mortality 2/2) response 1/1). Among these studies, LBD+ an additional -0.53 -2.9 MMSE points/year while one adjusted hazard ratio for 3.70. We conclude worse whether increased assessment scales.

Language: Английский

Citations

0
Non-motor asymmetry and dopamine degeneration in Parkinson’s disease DOI Creative Commons
Frederik Hansen, Karoline Knudsen, Malene Flensborg Damholdt

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 7(1)

Published: Dec. 24, 2024

Abstract Asymmetric dopaminergic degeneration of the striatum is a characteristic feature Parkinson’s disease, associated with right–left asymmetry in motor function. As such, studying provides insights into progressive neurodegeneration between cerebral hemispheres. Given impact Lewy pathology on various neurotransmitter systems beyond dopaminergic, it may be that other neuronal predominantly affected hemisphere are similarly affected. According to this hypothesis, would expected coincide systems. Consequently, functions primarily dependent integrity, such as function, should correlate bilateral non-motor rely systems, pupillary Therefore, study tested whether measures correlates striatal integrity. We also asymmetric greater overall. Using comparative cross-sectional design, we recruited newly diagnosed patients disease right-sided (n = 18), left-sided 15) or symmetric nigrostriatal denervation assessed dopamine PET. Detailed examinations lateralized function included lacrimation, hand skin wrinkling, salivation, olfaction and Healthy controls were for comparison. observed moderate-to-strong correlation putamen binding redilation speed [Spearman’s rank coefficient (rs) −0.53, 95% confidence interval (−0.77; −0.14), P 0.0084]. moderate correlations non-negative putaminal lacrimation [rs 0.35, (−0.00; 0.62), 0.0464] word recognition 0.36, (0.01; 0.63), 0.0410]. However, none significant after false discovery rate correction. group differences salivation (P 0.0390, ANOVA) trend towards participants loss compared healthy 0.0330, unadjusted). Additionally, showed greater, though non-significant, all those binding. In conclusion, contributes our understanding progression suggests link related autonomic particularly While findings do not support strict hemispheric association degeneration, potential relationships exist these features asymmetrical cholinergic.

Language: Английский

Citations

0